Generally, when a drug is administered into a living body, it reaches an affected site and exerts its pharmacological effects at that affected site, thereby exerting its therapeutic effects. On the other hand, it will not be therapeutic if the drug reaches tissues other than the affected site (that is, normal tissues).
Therefore, how to efficiently guide the drug to the affected site is important. A technique to guide the drug to the affected site is called drug delivery, which has been actively studied and developed in recent years. This drug delivery has at least two advantages. One advantage is that a sufficiently high drug concentration may be obtained at the affected tissue. Pharmacological effects will not be seen unless the drug concentration at the affected site is a constant value or more. The therapeutic effects cannot be expected if the concentration is low.
The second advantage is that the drug is guided to only the affected tissue and, therefore, adverse reactions to normal tissues may be inhibited.
Such drug delivery is most effective for cancer treatments by antitumor agents. Most antitumor agents inhibit the cell growth of cancer cells which divide actively, so that the antitumor agents will also inhibit the cell growth of even the normal tissues in which cells divide actively, such as the bone marrow, the hair roots, or the gastrointestinal mucosa.
Therefore, cancer patients to whom the antitumor agents are administered suffer adverse reactions such as anemia, hair loss, and vomiting. Since such adverse reactions impose heavy burdens on the patients, the dosage needs to be limited, thereby causing a problem of incapability to sufficiently obtain the pharmacological effects of the antitumor agents.
Alkylation antineoplastic agent among such antineoplastic agents is a generic term for antitumor agents having the ability to combine an alkyl group (—CH2—CH2—) with, for example, a nucleic acid protein. DNA is alkylated and DNA replication is inhibited, causing cell death. This action works regardless of cell cycles, also works on cells of the G0 period, has a strong effect on cells which grow actively, and tends to damage, for example, the bone marrow, the gastrointestinal mucosa, the germ cells, or the hair roots.
Moreover, antimetabolite antineoplastic agents are compounds having structures similar to those of nucleic acids or metabolites in a protein synthesis process, impairs cells by, for example, inhibiting synthesis of the nucleic acids, and specifically acts on the cells in mitotic phase.
Furthermore, antitumor antibiotics are chemical substances produced by microorganisms, have actions such as DNA synthesis inhibition and DNA strand breaking, and exhibit antitumor activity.
Also, microtubule inhibitors have antitumor effects by directly acting on microtubules that serve important roles to maintain normal functions of cells, for example, by forming spindles during cell division, placing intracellular organelles, and transporting substances. The microtubule inhibitors act on, for example, cells which divide actively, and nerve cells.
Moreover, platinum preparations inhibit DNA synthesis by forming DNA strands, interchain bonds, or DNA-protein bonds. Cisplatin is a representative drug, but it causes severe nephropathy and requires a large amount of fluid replacement.
Furthermore, parahormone antineoplastic agents are effective against hormone-dependent tumors. Female hormones or antiandrogens are administered to an androgen-dependent prostate cancer.
Also, molecular target drugs are used for treatments targeted at molecules that correspond to molecular biological characteristics specific to each malignant tumor.
Moreover, topoisomerase inhibitors are enzymes for temporarily generating breaks in DNA, and changing the number of tangles of DNA strands. Topoisomerase inhibitor I is an enzyme that generates breaks in one strand of a circular DNA, lets the other strand pass, and then closes the breaks; and topoisomerase inhibitor II is an enzyme that temporarily breaks both the two strands of the circular DNA, lets the other two DNA strands pass between the former two strands, and reconnects the broken strands.
Furthermore, nonspecific immunopotentiators inhibit cancer cell growth by activating the immune system.
An example of a specific method for drug delivery is the use of a carrier. This is to load the carrier, which tends to concentrate on the affected site, with the drug, and have the carrier carry the drug to the affected site.
A promising candidate for the carrier is a magnetic substance, and a method of attaching the carrier which is a magnetic substance, to the drug, and allowing the carrier to be accumulated at the affected site with a magnetic field is proposed (see, for example, Japanese Patent Application Laid-Open Publication No. 2001-10978).
However, when using the magnetic substance carrier as a carrier, it has been found that it is difficult to orally administer the magnetic substance carrier, carrier molecules are generally giant, and there are technical problems in the binding strength and affinity between the carrier and the drug molecules; and it has been difficult to put the magnetic substance carrier to practical use in the first place.
Therefore, the inventors of the present invention suggested a local therapeutic drug in which side chains for giving positive or negative spin charge density are bonded to a basic skeleton of an organic compound, and the local therapeutic drug in its entirety is suitably guided with an external magnetic field by sharing magnetism; and when the local therapeutic drug is applied to a human body or an animal, the local therapeutic drug is retained in the region where a magnetic field is applied locally by a magnetic field outside the body and medicinal effects that the local therapeutic drug originally possess, are exerted on the above region (WO 2008/001851). This therapeutic drug is auto-magnetic and does not rely on magnetic substance carriers. The publication discloses an iron-salen complex compound as one such drug. Japanese Patent Application Laid-Open Publication No. 2009-173631 discloses anti-tumor agents containing iron-salen complex compounds.
Furthermore, the inventors of the present application have proposed various medicines capable of binding, for example, medicinal molecules to a metal salen complex, and guiding them to a target region of an individual with a magnetic field (WO 2010/058280).